Evaluation of New Cone-beam Computed Tomographic Criteria for Radiographic Healing Evaluation after Apical Surgery: Assessment of Repeatability and Reproducibility.

INTRODUCTION Conventional 2-dimensional radiography uses defined criteria for outcome assessment of apical surgery. However, these radiographic healing criteria are not applicable for 3-dimensional radiography. The present study evaluated the repeatability and reproducibility of new cone-beam computed tomographic (CBCT)-based healing criteria for the judgment of periapical healing 1 year after apical surgery. METHODS CBCT scans taken 1 year after apical surgery (61 roots of 54 teeth in 54 patients, mean age = 54.4 years) were evaluated by 3 blinded and calibrated observers using 4 different indices. Reformatted buccolingual CBCT sections through the longitudinal axis of the treated roots were analyzed. Radiographic healing was assessed at the resection plane (R index), within the apical area (A index), of the cortical plate (C index), and regarding a combined apical-cortical area (B index). All readings were performed twice to calculate the intraobserver agreement (repeatability). Second-time readings were used for analyzing the interobserver agreement (reproducibility). Various statistical tests (Cohen, kappa, Fisher, and Spearman) were performed to measure the intra- and interobserver concurrence, the variability of score ratios, and the correlation of indices. RESULTS For all indices, the rates of identical first- and second-time scores were always higher than 80% (intraobserver Cohen κ values ranging from 0.793 to 0.963). The B index (94.0%) showed the highest intraobserver agreement. Regarding interobserver agreement, the highest rate was found for the B index (72.1%). The Fleiss' κ values for R and B indices exhibited substantial agreement (0.626 and 0.717, respectively), whereas the values for A and C indices showed moderate agreement (0.561 and 0.573, respectively). The Spearman correlation coefficients for R, A, C, and B indices all exhibited a moderate to very strong correlation with the highest correlation found between C and B indices (rs = 0.8069). CONCLUSIONS All indices showed an excellent intraobserver agreement (repeatability). With regard to interobserver agreement (reproducibility), the B index (healing of apical and cortical defects combined) and the R index (healing on the resection plane) showed substantial congruence and thus are to be recommended in future studies when using buccolingual CBCT sections for radiographic outcome assessment of apical surgery.

The contributions of the hippocampal formation, perirhinal cortex and areas TH/TF to object, spatial and contextual recognition memory in primates

Adult monkeys (Macaca mulatta) with lesions of the hippocampal formation, perirhinal cortex, areas TH/TF, as well as controls were tested on tasks of object, spatial and contextual recognition memory. ^ Using a visual paired-comparison (VPC) task, all experimental groups showed a lack of object recognition relative to controls, although this impairment emerged at 10 sec with perirhinal lesions, 30 sec with areas TH/TF lesions and 60 sec with hippocampal lesions. In contrast, only perirhinal lesions impaired performance on delayed nonmatching-to-sample (DNMS), another task of object recognition memory. All groups were tested on DNMS with distraction (dDNMS) to examine whether the use of active cognitive strategies during the delay period could enable good performance on DNMS in spite of impaired recognition memory (revealed by the VPC task). Distractors affected performance of animals with perirhinal lesions at the 10-sec delay (the only delay in which their DNMS performance was above chance). They did not affect performance of animals with areas TH/TF lesions. Hippocampectomized animals were impaired at the 600-sec delay (the only delay at which prevention of active strategies would likely affect their behavior). ^ While lesions of areas TH/TF impaired spatial location memory and object-in-place memory, hippocampal lesions impaired only object-in-place memory. The pattern of results for perirhinal cortex lesions on the different task conditions indicated that this cortical area is not critical for spatial memory. ^ Finally, all three lesions impaired contextual recognition memory processes. The pattern of impairment appeared to result from the formation of only a global representation of the object and background, and suggests that all three areas are recruited for associating information across sources. ^ These results support the view that (1) the perirhinal cortex maintains storage of information about object and the context in which it is learned for a brief period of time, (2) areas TH/TF maintain information about spatial location and form associations between objects and their spatial relationship (a process that likely requires additional time) and (3) the hippocampal formation mediates associations between objects, their spatial relationship and the general context in which these associations are formed (an integrative function that requires additional time). ^

Neonatal lead exposure impairs development of rodent barrel field cortex

Childhood exposure to low-level lead can permanently reduce intelligence, but the neurobiologic mechanism for this effect is unknown. We examined the impact of lead exposure on the development of cortical columns, using the rodent barrel field as a model. In all areas of mammalian neocortex, cortical columns constitute a fundamental structural unit subserving information processing. Barrel field cortex contains columnar processing units with distinct clusters of layer IV neurons that receive sensory input from individual whiskers. In this study, rat pups were exposed to 0, 0.2, 1, 1.5, or 2 g/liter lead acetate in their dam's drinking water from birth through postnatal day 10. This treatment, which coincides with the development of segregated columns in the barrel field, produced blood lead concentrations from 1 to 31 μg/dl. On postnatal day 10, the area of the barrel field and of individual barrels was measured. A dose-related reduction in barrel field area was observed (Pearson correlation = −0.740; P < 0.001); mean barrel field area in the highest exposure group was decreased 12% versus controls. Individual barrels in the physiologically more active caudoventral group were affected preferentially. Total cortical area measured in the same sections was not altered significantly by lead exposure. These data support the hypothesis that lead exposure may impair the development of columnar processing units in immature neocortex. We demonstrate that low levels of blood lead, in the range seen in many impoverished inner-city children, cause structural alterations in a neocortical somatosensory map.

Imaging neuroscience: Principles or maps?

This article reviews some recent trends in imaging neuroscience. A distinction is made between making maps of functional responses in the brain and discerning the rules or principles that underlie their organization. After considering developments in the characterization of brain imaging data, several examples are presented that highlight the context-sensitive nature of neuronal responses that we measure. These contexts can be endogenous and physiological, reflecting the fact that each cortical area, or neuronal population, expresses its dynamics in the context of interactions with other areas. Conversely, these contexts can be experimental or psychological and can have a profound effect on the regional effects elicited. In this review we consider experimental designs and analytic strategies that go beyond cognitive subtraction and speculate on how functional imaging can be used to address both the details and principles underlying functional integration and specialization in the brain.

The temporal lobe is a target of output from the basal ganglia.

The basal ganglia are known to receive inputs from widespread regions of the cerebral cortex, such as the frontal, parietal, and temporal lobes. Of these cortical areas, only the frontal lobe is thought to be the target of basal ganglia output. One of the cortical regions that is a source of input to the basal ganglia is area TE, in inferotemporal cortex. This cortical area is thought to be critically involved in the recognition and discrimination of visual objects. Using retrograde transneuronal transport of herpes simplex virus type 1, we have found that one of the output nuclei of the basal ganglia, the substantia nigra pars reticulata, projects via the thalamus to TE. Thus, TE is not only a source of input to the basal ganglia, but also is a target of basal ganglia output. This result implies that the output of the basal ganglia influences higher order aspects of visual processing. In addition, we propose that dysfunction of the basal ganglia loop with TE leads to alterations in visual perception, including visual hallucinations.

A complexity measure for selective matching of signals by the brain.

We have previously derived a theoretical measure of neural complexity (CN) in an attempt to characterize functional connectivity in the brain. CN measures the amount and heterogeneity of statistical correlations within a neural system in terms of the mutual information between subsets of its units. CN was initially used to characterize the functional connectivity of a neural system isolated from the environment. In the present paper, we introduce a related statistical measure, matching complexity (CM), which reflects the change in CN that occurs after a neural system receives signals from the environment. CM measures how well the ensemble of intrinsic correlations within a neural system fits the statistical structure of the sensory input. We show that CM is low when the intrinsic connectivity of a simulated cortical area is randomly organized. Conversely, CM is high when the intrinsic connectivity is modified so as to differentially amplify those intrinsic correlations that happen to be enhanced by sensory input. When the input is represented by an individual stimulus, a positive value of CM indicates that the limited mutual information between sensory sheets sampling the stimulus and the rest of the brain triggers a large increase in the mutual information between many functionally specialized subsets within the brain. In this way, a complex brain can deal with context and go "beyond the information given."

Binocular visual surface perception.

Binocular disparity, the differential angular separation between pairs of image points in the two eyes, is the well-recognized basis for binocular distance perception. Without denying disparity's role in perceiving depth, we describe two perceptual phenomena, which indicate that a wider view of binocular vision is warranted. First, we show that disparity can play a critical role in two-dimensional perception by determining whether separate image fragments should be grouped as part of a single surface or segregated as parts of separate surfaces. Second, we show that stereoscopic vision is not limited to the registration and interpretation of binocular disparity but that it relies on half-occluded points, visible to one eye and not the other, to determine the layout and transparency of surfaces. Because these half-visible points are coded by neurons carrying eye-of-origin information, we suggest that the perception of these surface properties depends on neural activity available at visual cortical area V1.

Layer-specific programs of development in neocortical projection neurons.

How are long-range axonal projections from the cerebral cortex orchestrated during development? By using both passively and actively transported axonal tracers in fetal and postnatal ferrets, we have analyzed the development of projections from the cortex to a number of thalamic nuclei. We report that the projections of a cortical area to its corresponding thalamic nuclei follow highly cell-specific programs of development. Axons from cells in the deepest layers of the cerebral cortex (layer 6 and superficial subplate neurons) appear to grow very slowly and be delayed for several weeks in the cerebral white matter, reaching the thalamus over a protracted period. Neurons of layer 5, on the other hand, develop their projections much faster; despite being born after the neurons of deeper layers, layer 5 neurons are the first to extend their axons out of the cortical hemisphere and innervate the thalamus. Layer 5 projections are massive in the first postnatal weeks but may become partly eliminated later in development, being overtaken in number by layer 6 cells that constitute the major corticothalamic projection by adulthood. Layer 5 projections are area-specific from the outset and arise as collateral branches of axons directed to the brainstem and spinal cord. Our findings show that the early development of corticofugal connections is determined not by the sequence of cortical neurogenesis but by developmental programs specific for each type of projection neuron. In addition, they demonstrate that in most thalamic nuclei, layer 5 neurons (and not subplate or layer 6 neurons) establish the first descending projections from the cerebral cortex.

Functional activation of the human ventrolateral frontal cortex during mnemonic retrieval of verbal information.

Regional cerebral blood flow was measured with positron emission tomography during the performance of a verbal free recall task, a verbal paired associate task, and tasks that required the production of verbal responses either by speaking or writing. Examination of the differences in regional cerebral blood flow between these conditions demonstrated that the left ventrolateral frontal cortical area 45 is involved in the recall of verbal information from long-term memory, in addition to its contribution to speech. The act of writing activated a network of areas involving posterior parietal cortex and sensorimotor areas but not ventrolateral frontal cortex.

Evidence for a hypothalamothalamocortical circuit mediating pheromonal influences on eye and head movements.

A method for simultaneous iontophoretic injections of the anterograde tracer Phaseolus vulgaris leukoagglutinin and the retrograde tracer fluorogold was used to characterize in the rat a hypothalamothalamocortical pathway ending in a region thought to regulate attentional mechanisms by way of eye and head movements. The relevant medial hypothalamic nuclei receive pheromonal information from the amygdala and project to specific parts of the thalamic nucleus reuniens and anteromedial nucleus, which then project to a specific lateral part of the retrosplenial area (or medial visual cortex). This cortical area receives a convergent input from the lateral posterior thalamic nucleus and projects to the superior colliculus. Bidirectional connections with the hippocampal formation suggest that activity in this circuit is modified by previous experience. Striking parallels with basal ganglia circuitry are noted.

Spreading and synchronization of intrinsic signals in visual cortex of macaque monkey evoked by a localized visual stimulus

Spatio-temporal maps of the occipital cortex of macaque monkeys were analyzed using optical imaging of intrinsic signals. The images obtained during localized visual stimulation (IS) were compared with the images obtained on presentation of a blank screen (IB). We first investigated spontaneous variations of the intrinsic signals by analyzing the 100 IBs for each of the three cortical areas. Slow periodical activation was observed in alternation over the cortical areas. Cross-correlation analysis indicated that synchronization of spontaneous activation only took place within each cortical area, but not between them. When a small, drifting grating (2degreesX2degrees) was presented on the fovea. a dark spot appeared in the optical image at the cortical representation of this retinal location. It spread bilaterally along the border between V1 and V2, continuing as a number of parallel dark bands covering a large area of the lateral surface of V1. Cross-correlation analysis showed that during visual stimulation the intrinsic signals over all of the three cortical areas were synchronized, with in-phase activation of V1 and V2 and anti-phase activation of V4 and V1/V2. The significance of these extensive synergistic and antagonistic interactions between different cortical areas is discussed. (C) 2003 Elsevier B.V. All rights reserved.

Specialization in pyramidal cell structure in the sensory-motor cortex of the chacma baboon (Papio ursinus) with comparative notes on macaque and vervet monkeys

The systematic study of pyramidal cell structure has revealed new insights into specialization of the phenotype in the primate cerebral cortex. Regional specialization in the neuronal phenotype may influence patterns of connectivity and the computational abilities of the circuits they compose. The comparative study of pyramidal cells in homologous cortical areas is beginning to yield data on the evolution and development of such specialized circuitry in the primate cerebral cortex. Recently, we have focused our efforts on sensory-motor cortex. Based on our intracellular injection methodology, we have demonstrated a progressive increase in the size of, the branching structure in, and the spine density of the basal dendritic trees of pyramidal cells through somatosensory areas 3b, 1, 2, 5, and 7 in the macaque and vervet monkeys. In addition, we have shown that pyramidal cells in premotor area 6 are larger, more branched, and more spinous than those in the primary motor cortex (MI or area 4) in the macaque monkey, vervet monkey, and baboon. Here we expand the basis for comparison by studying the basal dendritic trees of layer III pyramidal cells in these same sensory-motor areas in the chacma baboon. The baboon was selected because it has a larger cerebral cortex than either the macaque or vervet monkeys; motor cortex has expanded disproportionately in these three species; and motor cortex in the baboon reportedly has differentiated to include a new cortical area not present in either the macaque or vervet monkeys. We found, as in monkeys, a progressive increase in the morphological complexity of pyramidal cells through areas 3b, 5, and 7, as well as from area 4 to area 6, suggesting that areal specialization in microcircuitry was likely to be present in a common ancestor of primates. In addition, we found subtle differences in the extent of the interareal differences in pyramidal cell structure between homologous cortical areas in the three species. (c) 2005 Wiley-Liss, Inc.

Specializations of the granular prefrontal cortex of primates: Implications for cognitive processing

The biological underpinnings of human intelligence remain enigmatic. There remains the greatest confusion and controversy regarding mechanisms that enable humans to conceptualize, plan, and prioritize, and why they are set apart from other animals in their cognitive abilities. Here we demonstrate that the basic neuronal building block of the cerebral cortex, the pyramidal cell, is characterized by marked differences in structure among primate species. Moreover, comparison of the complexity of neuron structure with the size of the cortical area/region in which the cells are located revealed that trends in the granular prefrontal cortex (gPFC) were dramatically different to those in visual cortex. More specifically, pyramidal cells in the gPFC of humans had a disproportionately high number of spines. As neuron structure determines both its biophysical properties and connectivity, differences in the complexity in dendritic structure observed here endow neurons with different computational abilities. Furthermore, cortical circuits composed of neurons with distinguishable morphologies will likely be characterized by different functional capabilities. We propose that 1. circuitry in V1, V2, and gPFC within any given species differs in its functional capabilities and 2. there are dramatic differences in the functional capabilities of gPFC circuitry in different species, which are central to the different cognitive styles of primates. In particular, the highly branched, spinous neurons in the human gPFC may be a key component of human intelligence. (C) 2005 Wiley-Liss, Inc.

Causality and synchronisation in complex systems with applications to neuroscience

This thesis presents an investigation, of synchronisation and causality, motivated by problems in computational neuroscience. The thesis addresses both theoretical and practical signal processing issues regarding the estimation of interdependence from a set of multivariate data generated by a complex underlying dynamical system. This topic is driven by a series of problems in neuroscience, which represents the principal background motive behind the material in this work. The underlying system is the human brain and the generative process of the data is based on modern electromagnetic neuroimaging methods . In this thesis, the underlying functional of the brain mechanisms are derived from the recent mathematical formalism of dynamical systems in complex networks. This is justified principally on the grounds of the complex hierarchical and multiscale nature of the brain and it offers new methods of analysis to model its emergent phenomena. A fundamental approach to study the neural activity is to investigate the connectivity pattern developed by the brain’s complex network. Three types of connectivity are important to study: 1) anatomical connectivity refering to the physical links forming the topology of the brain network; 2) effective connectivity concerning with the way the neural elements communicate with each other using the brain’s anatomical structure, through phenomena of synchronisation and information transfer; 3) functional connectivity, presenting an epistemic concept which alludes to the interdependence between data measured from the brain network. The main contribution of this thesis is to present, apply and discuss novel algorithms of functional connectivities, which are designed to extract different specific aspects of interaction between the underlying generators of the data. Firstly, a univariate statistic is developed to allow for indirect assessment of synchronisation in the local network from a single time series. This approach is useful in inferring the coupling as in a local cortical area as observed by a single measurement electrode. Secondly, different existing methods of phase synchronisation are considered from the perspective of experimental data analysis and inference of coupling from observed data. These methods are designed to address the estimation of medium to long range connectivity and their differences are particularly relevant in the context of volume conduction, that is known to produce spurious detections of connectivity. Finally, an asymmetric temporal metric is introduced in order to detect the direction of the coupling between different regions of the brain. The method developed in this thesis is based on a machine learning extensions of the well known concept of Granger causality. The thesis discussion is developed alongside examples of synthetic and experimental real data. The synthetic data are simulations of complex dynamical systems with the intention to mimic the behaviour of simple cortical neural assemblies. They are helpful to test the techniques developed in this thesis. The real datasets are provided to illustrate the problem of brain connectivity in the case of important neurological disorders such as Epilepsy and Parkinson’s disease. The methods of functional connectivity in this thesis are applied to intracranial EEG recordings in order to extract features, which characterize underlying spatiotemporal dynamics before during and after an epileptic seizure and predict seizure location and onset prior to conventional electrographic signs. The methodology is also applied to a MEG dataset containing healthy, Parkinson’s and dementia subjects with the scope of distinguishing patterns of pathological from physiological connectivity.

Investigating the functional properties of the somatosensory cortex during experimental visceral pain using magnetoencephalography

Background The somatosensory cortex has been inconsistently activated in pain studies and the functional properties of subregions within this cortical area are poorly understood. To address this we used magnetoencephalography (MEG), a brain imaging technique capable of recording changes in cortical neural activity in real-time, to investigate the functional properties of the somatosensory cortex during different phases of the visceral pain experience. Methods In eight participants (4 male), 151-channel whole cortex MEG was used to detect cortical neural activity during 25 trials lasting 20 seconds each. Each trial comprised four separate periods of 5 seconds in duration. During each of the periods, different visual cues were presented, indicating that period 1=rest, period 2=anticipation, period 3=pain and period 4=post pain. During period 3, participants received painful oesophageal balloon distensions (four at 1 Hz). Regions of cortical activity were identified using Synthetic Aperture Magnetometry (SAM) and by the placement of virtual electrodes in regions of interest within the somatosensory cortex, time-frequency wavelet plots were generated. Results SAM analysis revealed significant activation with the primary (S1) and secondary (S2) somatosensory cortices. The time-frequency wavelet spectrograms showed that activation in S1 increased during the anticipation phase and continued during the presentation of the stimulus. In S2, activation was tightly time and phase-locked to the stimulus within the pain period. Activations in both regions predominantly occurred within the 10–15 Hz and 20–30 Hz frequency bandwidths. Discussion These data are consistent with the role of S1 and S2 in the sensory discriminatory aspects of pain processing. Activation of S1 during anticipation and then pain may be linked to its proposed role in attentional as well as sensory processing. The stimulus-related phasic activity seen in S2 demonstrates that this region predominantly encodes information pertaining to the nature and intensity of the stimulus.